1. Field of the Invention
The present invention relates to a living body information measuring apparatus for optically measuring non-invasively a concentration of a substance in the blood or in the body fluid in the biological tissue cell or outside the biological tissue cell, or opt-physical information of the biological tissue for health care, diagnosis or treatment of diseases, or beauty care, particularly relates to a biological information measuring apparatus for non-invasively measuring information with regard to blood composition concentration of glucose, cholesterol, neutral fat, proteins such as albumin, hemoglobin, and creatine or the like, body gas concentration of oxygen or carbon dioxide, concentration of alcohol, a drug or the like, or information with regard to denaturing the biological tissue represented by cancer, inflammation, skin moisture holding function, arteriosclerosis or the like by using visible light, near infrared light, or middle infrared light or the like.
2. Description of the Related Art
As a representative background art apparatus for measuring a composition or a concentration of a substance present in a subject, there is a blood glucose meter for measuring a glucose concentration (blood glucose value) in the blood or in the body fluid. Currently, a widely used blood glucose meter utilizes a small amount of blood sample sampled by piercing a needle to a portion of the finger, the arm or the like of the subject and a concentration thereof is measured by chemically reacting glucose in the sampled blood.
Further, as the most general method of measuring the glucose concentration, there is a method of using an enzyme electrode. As an enzyme used in detecting glucose, there is, for example, glucose oxidase (GOD). By fixing the enzyme to a polymer film or the like and bringing glucose in the substance of the subject into contact with the GOD fixed film, oxygen is consumed, and the glucose concentration can be measured by detecting a change in the enzyme. The blood glucose meter of the blood sampling type is constituted by a portable size and is utilized for monitoring the blood glucose level of a diabetic patient.
However, according to the above-described method, it is necessary to pierce a needle to a portion of the finger, the arm or the like for sampling the blood, the skin of the subject is damaged and the subject is accompanied by pain. Therefore, although it is preferable to carry out measurement by 5 times or more per day for strictly controlling the blood glucose level of the diabetic patient, in a current state, a number of times of measurement stay to be typically 2 or 3 times per day.
There is investigated a method of sampling and measuring a small amount of the interstitial fluid by opening a small hole to a degree of not being accompanied by pain on a surface of the skin by using a small needle or laser, or a method of sampling and measuring an effluent solution of the interstitial fluid or the like by improving effluent permeability of the skin by applying voltage or ultrasonic wave to the surface of the skin with an object of alleviating the damage of the skin or the pain of the patient.
On the other hand, as a method of non-invasively measuring a component or a concentration of a substance present in the subject of glucose or the like without necessitating to sample the blood or sample the interstitial fluid, a method of utilizing an electromagnetic wave is known (for example, JP-B-5-58735 (pages 3-5, FIGS. 1-5)).
The method is a method of measuring a composition or a concentration of a substance present in the subject by irradiating the surface of the skin of the subject or the like with a plurality of different wavelengths of near infrared light, classifying detecting signals thereof into a reference signal and a measuring signal and operating to process values thereof. Here, an electromagnetic wave having a wavelength band of about 380 through 770 nm is defined as visible light, an electromagnetic wave having a wavelength band of about 770 through 2500 nm is defined as near infrared light, an electromagnetic wave having a wavelength band of about 2500 through 25000 nm is defined as middle infrared light and an electromagnetic wave having a wavelength band of about 25 through 100 μm is defined as far infrared light.
In the above-described method, as a light source of near infrared light, there is used a method of spectroscopically dividing light emitted from a white light source of tungsten-halogen lamp or the like into a prescribed wavelength by spectroscopic means of an interference filter or the like, monochromatic light or a semiconductor laser (LD) or a light emitting diode (LED) for emitting light near to monochromatic light. Further, as a detector of near infrared light transmitted and diffused in the subject, an optical detector such as photodiode (PD) is used.
The above-described non-invasive spectroscopic analysis of the biological substance using near infrared light, or further, visible light is a method attracting attention in recent years, and is provided with an advantage that an aqueous solution system can be analyzed and a function of permeating the organism is high since absorption of water occupying a large portion as a constituent element of the organism is small in comparison with the spectroscopic analysis using middle or far infrared light. On the other hand, the analysis has a disadvantage that a signal ascribed to molecular vibration is about one hundredth as small as a middle infrared light region and ascription of the signal is difficult to be specified.
Further, also in measurement using near infrared light, according to near infrared light in a region near first harmonic of water (1250 through 1800 nm), a spectral signal ascribed to molecular vibration is comparatively large, on the other hand, transmittivity of light is poor, and near infrared light in a region near second harmonic of water (800 through 1300 nm) is provided with a characteristic that a spectral signal ascribed to molecular vibration is small, on the other hand, transmittivity of light is excellent.
That is, when a signal of a biologic substance constituting an object thereof is detected in a near infrared region, a problem occurs in that there are a number of cases in which a signal in correspondence with a change in a concentration of the biological substance constituting the object is very small and ascription of the signal is not clear. As a method of resolving such a problem, there is a statistically analyzing method, or multivariate analyzing method (refer to, for example, JP-A-10-325794 (pages 4-9, FIGS. 1-8)).
Although the analyzing methods are excellent methods in detecting a small change in a signal and accurately quantifying a substance, the methods do not improve a signal to noise ratio (SN ratio) of a signal constituting an index of biological substance information constituting the object.
As a method of improving the SN ratio, there is used a method of making a change (variation) in a concentration of a biological substance constituting the object clear by calculating a difference between a reference signal and a signal related to substance information constituting the object, or a ratio thereof, or a method of reducing a noise component by averaging signals measured by a plurality of times.
Further, when light transmitted and diffused in the subject tissue by irradiating light to the subject is detected, there is a case in which noise is increased by superposing and measuring light which is not related to information constituting an index of a condition of the tissue scattered or reflected at a surface of the tissue of the subject or input and output portions of light of a measuring instrument other than an optical signal having information constituting the index of the condition of the tissue of the subject.
As a measuring method for resolving such a problem, there is a local diffuse reflectance method for calculating a light absorbing degree of a substance from a plurality of measured data substantially having different diffusion light optical path lengths by changing a distance between an irradiating point and a light receiving point (refer to, for example, International Publication W099/59464 (page 7, FIG. 1)).
According to the method, a plurality of optical fibers are brought into direct contact with a surface of a measuring portion of a subject, light is detected at a plurality of portions in which irradiating positions and light detecting positions spatially differ from each other and therefore, detection of a noise signal generated by scattering or reflecting light at the surface of the tissue of the subject or at input and output sites of light of the measuring instrument can be restrained.
Further, there is also disclosed a method of constituting a plurality of light sources and detectors in a shape of an array and irradiating and receiving light by way of an optical fiber plate (refer to, for example, specification of U.S. Pat. No. 5,893,364 (pages 7-8, FIGS. 1-2)).
An optical characteristic of the tissue of the organism differs by an individual difference or a region. The difference in the optical characteristic effects a significant influence on measuring accuracy. For example, when there is the blood vessel or the like in an optical path, an optical signal is varied by an influence of beat of the blood. As a method constituting an object by achieving promotion of measuring accuracy by restraining the optical characteristic influence which differs by the individual difference or the region, there is a method of accurately sampling desired information reflected with a condition of the tissue of the subject by irradiating a plurality of wavelengths of light, collecting an optical signal diffused, transmitted or reflected in the subject at that occasion and carrying out processing of cross correlation or the like from the information (refer to, for example, JP-A-10-325794 (pages 4-9, FIGS. 1-8)).
Further, as a method of restraining influence of a difference of an optical characteristic by a difference by positions, there is disclosed a method of taking an image of a portion of a subject including a portion to be irradiated with light to constitute image information by using an image taking element of a charge coupled device or the like and controlling a position of irradiating light to be the same at each time of measurement from the image information (refer to, for example, JP-A-11-128176 (pages 2-4, FIGS. 1-2)).
Further, it has been clarified that a measurement result is varied depending on a temperature of a portion to be measured and as a method of resolving the problem, there is disclosed a method of controlling a temperature of the measured site, a method of measuring and correcting a temperature of the measured site (refer to, for example, JP-A-11-123195 (pages 3-4, FIGS. 4-8)).
Further, in order to efficiently make light invade inside of the subject and promote a function of detecting light reaching outside of the subject by being diffused, transmitted or reflected in the subject, there is also a method of improving a performance of bringing a subject and a measuring apparatus into contact with each other by using a manchette (compressing band) utilized in a blood pressure meter or the like at input and output portions of light and vicinities thereof.
With regard to a non-invasive measurement of a composition or a concentration of a substance present in the subject other than a glucose concentration (blood glucose value), for example, an apparatus of measuring a hemoglobin concentration in the capillary, an apparatus for measuring an oxygen saturation degree or the like has been put into practice. Further, it is desired to develop an apparatus of non-invasively and quantitatively measuring various kinds of biological information starting from cholesterol to neutral fat which are important organism substances related to life-style related diseases similar to glucose.
In an apparatus optically measuring and analyzing noninvadingly information with regard to a composition or a concentration of a substance present in a subject, or denaturing the subject tissue, a problem arises in that a measured position or a measuring condition of a subject is varied at each measurement, a measurement result differs depending on a position of a measured portion owing to a difference of the tissue of the subject or the like.